This invention relates to membrane filtration of matter from liquid suspensions, and particularly to biomedical applications of such technology. It is especially relevant to, but not limited to, the separation or fractionation of the constituents of blood.
Techniques for the separation and collection of given constituents of whole blood are in wide use for many therapeutic, medical and experimental applications. Plasmapheresis (the separation of fluid plasma from the red and white cells of whole blood) forms the basis of widespread plasma storage and supply systems, and also is employed increasingly in therapeutic apheresis. Plasma is collected from individual donors by withdrawing whole blood, separating the plasma, and preferably returning high hematocrit (high cell percentage) fractions back to the donor. Plasmapheresis by centrifugal separation is widely used in laboratories but is essentially a batch process of limited convenience and commercial practicality. Continuous centrifugal separation is desired if plasma is to be collected rapidly and with minimum donor inconvenience, and in the modern state of the art this cannot be done at reasonable cost. Blood handling and collection systems must be completely sterile, which in effect requires that all elements in contact with the blood be low cost disposable components or devices. Many workers in the art have thus experimented with membrane filtration techniques, in which a membrane with suitably small pore size (e.g. 0.5 microns) is utilized to filter plasma from the blood. Because of the viscous and complex quality of whole blood, simple filtration does not suffice because deposition (clogging of pores with cellular matter) quickly decreases the efficiency of transfer through the membrane.
Recognizing these problems, a number of workers in the art have sought to utilize the shear principle so as to increase efficiency. Transport of whole blood laterally across a membrane surface which is moving relative to an opposed surface sets up shearing forces on the blood sheet, tending to keep the cellular matter in motion and to lift it away from the membrane pores, substantially reducing the deposition problem. Workers in the art have observed a generally increasing relationship between the amount of shear and the efficiency of the filtration process, with an upper limit being imposed by unwanted cell disruption or hemolysis, typically at maximum shear rates of 7,500 to 10,000/sec with prior devices.
Membrane filtration effectively appeared to have reached a practical limit with various flat membrane configurations, because of various pressure losses and flow discontinuities. In practice, a substantial membrane area has been required for such configurations, in order to enable plasma collection at a reasonable rate from an individual donor. However the membrane cost is high and the system efficiency decreases with the duration of usage. Thus the desirable objective of a low cost disposable has not been heretofore achieved with a reliably operating system.
More recently, however, a remarkable advance in blood separation technology using membrane filtration has arisen from a different structure, described in patent application Ser. No. 449,470, filed Dec. 13, 1982, by Halbert Fischel and having a common assignee. The configuration described in that patent application provides filtration rates in excess of ten times that found in prior membrane filtration devices, for a given surface area. A membrane covered spinner, having an interior collection system, is disposed within a stationary shell, and blood is fed into the space between the spinner and the shell, moving both circumferentially about the shell and along the longitudinal axis to a spaced apart exit region. A practical device, having a gap of 0.030" and a rotational velocity of approximately 3600 r.p.m., with a spinner diameter of 1" (2.54 cm) and length of 3" (7.5 cm) enables plasma to be derived at approximately 45 ml/min, and with high plasma recovery (e.g. in excess of 70%). A plasma recovery of 0.9 ml/cm.sup.2 /min is achieved in contrast to prior art flat plate systems providing about 0.039 ml cm.sup.2 /min and hollow fiber systems providing 0.-013 ml cm.sup.2 /min. The significant improvement in filtration efficiency thus afforded makes a low cost plasmapheresis disposable practical for the first time, and enables two to three units of blood to be transferred conveniently and quickly as high hematocrit remainder is returned to the donor.
While flow conditions existing between a rotating spinner and a concentric shell have been much studied, being termed Couette flow, the extraction of a filtrate through a membrane on the spinner represents a special case of potentially wide applicability. Generically, this configuration encompasses a number of systems in which a filter member spinning within a bath is used to prevent or limit particulates in the bath from adhering to the filter, while drawing filtrate into the interior of the spinner. Particular examples of these are shown in an article by M. Lopez-Leiva entitled "Ultrafiltration at Low Degrees of Concentration Polarization: Technical Possibilities" in Desalination (Netherlands) Vol. 35, pp. 125-128 (1980) dealing with the concentration of milk products, and in U.S. Pat. No. 4,184,952 (Shell Oil) dealing with the extraction of oil from basic sediment and water. However, there is nothing in these disclosures that would tend to indicate that the significant improvement achieved by Fischel in plasmapheresis would even be possible, or explain the mechanism of separation in such a system. The Fischel patent application as filed hypothesized that a "shear centrifugation" effect takes place, with centrifugal forces acting to cause migration of the cellular matter outwardly toward the stationary wall, while a plasma-rich layer resides at the surface. Limiting factors on the performance of this system were described in terms of conditions to maintain laminar flow between the spinner and the outer wall, while also exerting sufficient centrifugal force to achieve outward cell migration. Thus the application purported to distinguish from other rotating flow systems in which relative movement between two concentric cylinders causes creation of localized cellular structures, called Taylor vortices, between the walls.
Taylor vortices also have been intensively investigated in the literature and a number of devices, particularly oxygenators proposed by Brumfield, in U.S. Pat. Nos. 3,771,658, 3,771,899 and 4,212,241, have been considered that utilize such effects. Most of the investigations of Taylor vortices are concerned with theoretical aspects, and few systems, including the oxygenators, have been successfully implemented using these principles. No systems using Taylor vortices are known in which the dynamics of the fluid medium between the members are affected or altered by continuous extraction of constituents from the medium.
The situation in which a filtrate is extracted from a complex fragile living system, such as whole blood, can be seen to involve many complex factors. It is shown hereafter that the operating mode in the Fischel system does not create laminar flow under the conditions stated above, and that the withdrawal of the plasma itself generates forces substantially in excess of the centrifugal forces acting on the blood cells. While the particular plasmapheresis system of Fischel functions with the efficiency described, further improvements as to the limits and optimums of the process are made feasible by the use of configurations and operating conditions which take into account all of the dominant system requirements to establish and enhance a substantially different mode of operation.